Neuronal Migration Disorder is a heterogeneous group of disorders that is caused by the abnormal migration of neurons in the developing brain and nervous system. Neuron migration occurs as early as the second month of gestation, and is controlled by a complex assortment of chemical guides and signals (1)

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Neurol migration which can occur as early as the second month of gestation is controlled by an assortment of chemical guides and signals. ​ When these signal are either absent or incorrect, neuron will not end where they belong.

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**Causes**

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Neuronal Migration Disorders may be caused by genetic or biochemical abnormalities. Several genetic abnormalities have been identified, including a deletion of a gene on chromosome which causes lissencephaly and a mutation of a gene on chromosome, which causes lissencephaly in males and band heterotopia in females.

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Other genes have been implicated as well.

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The most well characterized genes include DCX on the X chromosome, responsible for double cortex syndrome, and LIS1 on chromosome 17, the first gene identified for lissencephaly. Cobblestone lissencephaly is associated with abnormalities in fukutin, a gene responsible for Fukuyama muscular dystrophy, a syndrome consisting of muscle weakness and cobblestone lissencephaly. Periventricular heterotopia is associated with abnormalities of the filamin1 gene on the X chromosome. DCX, LIS1, and filamin1 are genes responsible for controlling the mechanics of cell movement during neuronal migration. Schizencephaly has been associated with abnormalities in EMX2, a transcription factor gene whose role in neuronal migration is as yet unidentified. Neuronal migration disorders can also be associated with early insults to the brain from infections or damage from stroke. (2)

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**Symptoms**

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Symptoms of this disorder may include hypotonia (reduced muscle tone), seizures, developmental delay, mental retardation,​ growth failure, feeding difficulties,​ microcephaly,​ and motor dysfunction. Most children with an NMD appear normal, but some disorders have characteristic facial or skull features that can be recognized by a neurologist. ​

Neuroimaging. CT-Scan or MRI of the brain will show the characteristic abnormality. MRI has better resolution and may detect polymicrogyria or small heterotopias more easily than CT-Scan. Genetic testing is available for patients with lissencephaly to identify whether the genes are defective.

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**Complications**

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Some specific disorders considered as alterations in neuronal migration are lissencephaly,​ schizencephaly,​pachygyria,​ polymicrogyria and focal cortical dysplasia, while the Miller-Dieker syndrome, muscle-brain-eye syndrome, Fukuyama congenital muscular dystrophy and Walker Warburg syndrome are genetic disorders associated with this malformations. ​

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**Treatment**

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There is no “cure” for neuronal migration disorder at the present time. Treatments would focus on the co-morbidities and/or complications.

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For example manual decongestive therapy and the wearing of compression garments would be the standard for the management and the treatment of lymhpedema.

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Anti-seizure medication may be indicated, as well as various types of special education consisting of physical, speech and occupational therapies.

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**Prognosis**

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The prognosis for Neuronal Migration Disorder depends on the specific disorder and degree of brain abnormality and neurological signs and symptoms.(1)

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For individuals with severe malformation,​ such as classical lissencephaly or bilateral schizencephaly will die at an early age due to failure to thrive orinfections such as pneumonia. ​

1] Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China. [2] Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China. [3] State Key Laboratory of Molecular Neuroscience,​ The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China. [4].

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**Abstract**

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Disrupted cortical neuronal migration is associated with epileptic seizures and developmental delay. However, the molecular mechanism by which disruptions of early cortical development result in neurological symptoms is poorly understood. Here we report α2-chimaerin as a key regulator of cortical neuronal migration and function. In utero suppression of α2-chimaerin arrested neuronal migration at the multipolar stage, leading to accumulation of ectopic neurons in the subcortical region. Mice with such migration defects showed an imbalance between excitation and inhibition in local cortical circuitry and greater susceptibility to convulsant-induced seizures. We further show that α2-chimaerin regulates bipolar transition andneuronal migration through modulating the activity of CRMP-2, a microtubule-associated protein. These findings establish a new α2-chimaerin-dependent mechanism underlying neuronal migration and proper functioning of the cerebral cortex and provide insights into the pathogenesis of seizure-related neurodevelopmental disorders.

Complex neuropsychiatric disorders are believed to arise from multiple synergistic deficiencies within connected biological networks controlling neuronal migration, axonal pathfinding and synapse formation. Here, we show that deletion of 14-3-3ζ causes neurodevelopmental anomalies similar to those seen in neuropsychiatric disorders such as schizophrenia,​ autism spectrum disorder and bipolar disorder. 14-3-3ζ-Deficient mice displayed striking behavioural and cognitive deficiencies including a reduced capacity to learn and remember, hyperactivity and disrupted sensorimotor gating. These deficits are accompanied by subtle developmental abnormalities of the hippocampus that are underpinned by aberrant neuronalmigration. Significantly,​ 14-3-3ζ-deficient mice exhibited abnormal mossy fibre navigation and glutamatergic synapse formation. The molecular basis of these defects involves the schizophrenia risk factor, DISC1, which interacts isoform specifically with 14-3-3ζ. Our data provide the first evidence of a direct role for 14-3-3ζ deficiency in the aetiology of neurodevelopmental disorders and identifies 14-3-3ζ as a central risk factor in the schizophrenia protein interaction network.Molecular Psychiatry advance online publication,​ 29 November 2011; doi:​10.1038/​mp.2011.158.

We have only just begun to decipher the complexity of our brain, including its maturation. Correct brain development and communication among brain areas are crucial for proper cognitive behavior. Brain area-specific genes expressed within a particular time window direct neurodevelopmental events such as proliferation,​ migration, axon guidance, dendritic arborization,​ and synaptogenesis. ​

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These genes can pose as susceptibility factors in neurodevelopmental disorderseventually resulting in area-specific cognitive deficits. Therefore, in utero electroporation (IUE)-mediated gene transfer can aid in creating valuable animal models in which the regionality and time of expression can be restricted for the targeted gene(s). Moreover, through the use of cell-type-specific molecular constructs, expression can be altered in a particularneuronal subset within a distinct area such that we are now able to causally link the function of that gene in that brain region to the etiology of the disorder. Thus, IUE-mediated gene transfer is an attractive molecular technique to spatiotemporally address the developmental aspects of gene function in relation to neurodevelopmental disorder-associated endophenotypes

[[ http://​www.landesbioscience.com/​journals/​cc/​article/​17953/​ |Bioenergy sensing in the brain: the role of AMP-activated protein kinase in neuronal metabolism, development and neurological diseases.]] Oct 2011